The guidance of visual attention in humans and non-human primates

The guidance of visual attention in humans and non-human primates is thought to be controlled by a frontoparietal network of brain areas including the dorsolateral prefrontal (dlPFC) and posterior parietal (PPC) cortex (Corbetta & Shulman, 2002; Schall, Alectinib cell line 2002; Bisley & Goldberg, 2010). PPC and dlPFC neurons share many properties, including

large receptive fields and greatly enhanced responses to attended than to unattended stimuli (Schall & Hanes, 1993; Constantinidis & Steinmetz, 2001; Katsuki & Constantinidis, 2012b). Traditionally, PPC has been thought to be relatively more important in the processing of bottom-up information for the determination of visual saliency and PFC has been thought of as the source of top-down information (Buschman & Miller, 2007; Ibos et al., 2013). This dichotomy has been challenged by some studies suggesting similar courses of activation in posterior parietal Pexidartinib research buy areas, such as the lateral intraparietal area (LIP) and area 7a, and prefrontal areas, such as area 46 and the frontal eye field (FEF) of dlPFC, in behavioral tasks requiring bottom-up attention (Thompson et al., 1996; Thomas & Pare, 2007; Katsuki

& Constantinidis, 2012a; Purcell et al., 2013). A recent study revealed that dlPFC represents a stimulus that attracts attention by bottom-up factors alone no later than PPC even though the initial visual response latency of neurons was shorter in PPC than dlPFC (Katsuki & Constantinidis, 2012a). These results suggest an early involvement of dlPFC in

the representation of bottom-up saliency, raising the possibility that behavioral choices are shaped jointly by the activity in the two areas. Evidence in support of this view suggests that activity of both PFC and PPC neurons can bias behavioral choice and performance in a motion discrimination task and visual search tasks (Thompson et al., Janus kinase (JAK) 2005; Hanks et al., 2006; Heitz et al., 2010). However, parallel time courses of stimulus representation do not necessarily imply identical roles for the two areas in the guidance of visual attention. Distinct neurophysiological patterns of responses between dlPFC and PPC have been described with respect to the representation of distracting stimuli, with dlPFC being better able to filter distractors (Qi et al., 2010; Suzuki & Gottlieb, 2013). Different behavioral effects have also been demonstrated after reversible inactivation of each area, where inactivation of PFC affected both easy and difficult search performance while inactivation of PPC affected only difficult search performance (Wardak et al., 2004, 2006). Activity in the two areas may still be specialized on different respects of guidance of attention. We therefore tested whether behavior correlated with neuronal activity, equally for PPC and dlPFC.

The lateral cortex containing TOM+ pyramidal neurons and GAD65-GF

The lateral cortex containing TOM+ pyramidal neurons and GAD65-GFP+ interneurons were trypsinised in Hanks’ medium for 10 min at 37 °C. After centrifugation the pellet was filtered using 40-μm-pore filters (Falcon). GFP+ and TOM+ cells were sorted using fluorescence-activated cell sorting (FACS). Total RNA from the sorted cells was extracted, amplified (MessageAMP™ II

aRNA Amplification kit; Ambion, Zug, Switzerland) in order to obtain at least 50 ng of RNA, and converted into cDNA. PCR was done using a REDtaq Ready-Mix (Sigma, Buchs, Switzerland) and PCR products were electrophoresed in a 2% agarose gel. For quantitative PCR, PCR reactions were performed in triplicate on cDNA from TOM+ cells and GAD65-GFP+ cells using SYBR green PCR Master Mix (Applied Biosystems, Rotkreuz, Switzerland) in an ABI Prism 7900 Sequence Detection system (Applied Biosystems).

Four genes were used as internal controls: beta-actin (actb), gamma-actin (actg1), eukaryotic elongation factor-1 (eef1a1) and beta-glucuronidase (Gusb). Primers for the different adrenergic receptors were designed using BMS-354825 ic50 the Ensembl database and the Primer3 software. Primer sequences were as follows: adra1a forward, 5′-CTGCCATTCTTCCTCGTGAT-3′ and reverse 5′-GCTTGGAAGACTGCCTTCTG-3′, adra1b, forward, 5′-AACCTTGGGCATTGTAGTCG-3′ and reverse 5′-CTGGAGCACGGGTAGATGAT-3′ adra1d forward, 5′-TCCGTAAGGCTGCTCAAGTT-3′ and reverse, 5′-CTGGAGCAGGGGTAGATGAG-3′, adra2a forward, 5′ TGCTGGTTGTTGTGGTTGTT-3′ and reverse, 5′-GGGGGTGTGGAGGAGATAAT-3′, adra2b, forward 5′-GCCACTTGTGGTGGTTTTCT-3′, reverse, 5′- TTCCCCAGCATCAGGTAAAC-3′, adra2c forward, 5′-TCATCGTTTTCACCGTGGTA-3′ and reverse, 5′-GCTCATTGGCCAGAGAAAAG-3′, adrb1 forward, 5′-TCGCTACCAGAGTTTGCTGA-3′ and reverse, 5′-GGCACGTAGAAGGAGACGAC-3′, adrb2, forward. 3-oxoacyl-(acyl-carrier-protein) reductase 5′-GACTACACAGGGGAGCCAAA-3′, and reverse, 5′-TGTCACAGCAGAAAGGTCCA-3′, adrb3 forward, 5′-TGAAACAGCAGACAGGGACA-3′,

reverse 5′-TCAGCTTCCCTCCATCTCAC-3′. Cortical slices were imaged in a thermoregulated chamber maintained at 37 °C and CO2 at 5% as previously described (Riccio et al., 2009). Time-lapse movies were acquired in parallel using two fluorescent microscopes (Eclipse TE2000; Nikon, Egg, Switzerland) equipped with a Nikon Plan 10×/0.30 objective connected to a digital camera (Retiga EX). Time-lapse imaging was performed 3–4 h after slice preparation over a period of 24 h. Images were acquired using the Open-lab software (version 5.0; Schwerzenbach, Switzerland) every 5 min for 200 min in short time-lapse sequences and for 600 min in washout experiments. A control time-lapse sequence of 95 min was acquired in each condition before the treatment condition. Time-lapse stacks were generated and analysed using Metamorph software (version 7.4; Visitron, Puchheim, Germany).

Movie S4 Long-term activation of adra2 with medetomidine affects

Movie S4. Long-term activation of adra2 with medetomidine affects interneuron migration. Time-lapse movie showing migrating GAD65-GFP positive cells under control conditions ascending from the intermediate buy BYL719 zone towards the cortical plate (white arrows). After long-term adra2 activation (medetomidine 500 mM; blue arrows) cells are persistently halted in their migration. Movie S5. Effects of adra2

activation on interneuron migration are reversible. Time-lapse movie showing migrating GAD65-GFP positive cells under control conditions ascending from the intermediate zone towards the cortical plate (white arrows). After adra2 activation (medetomidine 500 mM;

light SGI-1776 cell line blue arrows) cells are halted in their migration but this effect is reversible after removal of the drug (dark blue arrows). As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer-reviewed and may be re-organized for online delivery, but are not copy-edited or typeset by Wiley-Blackwell. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. “
“Neurotransmitters diffuse out of the synaptic cleft and act on adjacent synapses to exert concerted control of the

synaptic strength within neural pathways that converge on single target neurons. The excitatory transmitter released from climbing fibers (CFs), presumably glutamate, is shown to inhibit γ-aminobutyric acid (GABA) release at basket cell (BC)–Purkinje cell (PC) synapses in the rat cerebellar cortex through its extrasynaptic diffusion and activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors PIK3C2G on BC axon terminals. This study aimed at examining how the CF transmitter-diffusion-mediated presynaptic inhibition is controlled by glutamate transporters. Pharmacological blockade of the PC-selective neuronal transporter EAAT4 markedly enhanced CF-induced inhibition of GABAergic transmission. Tetanic CF-stimulation elicited long-term potentiation of glutamate transporters in PCs, and thereby attenuated the CF-induced inhibition. Combined use of electrophysiology and immunohistochemistry revealed a significant inverse relationship between the level of EAAT4 expression and the inhibitory action of CF-stimulation on the GABA release at different cerebellar lobules – the CF-induced inhibition was profound in lobule III, where the EAAT4 expression level was low, whereas it was minimal in lobule X, where EAAT4 was abundant.

7,8 The use of such simple measures by long-term travelers is sub

7,8 The use of such simple measures by long-term travelers is suboptimal at best.9 Adherence to chemoprophylaxis is poor among long-term travelers, mainly due to the side effects of the drugs, fear of adverse consequences of long-term use, and conflicting advice on long-term prophylaxis.10–14 Bcl-2 inhibitor Despite the increased incidence of malaria in long-term travelers, research about risk factors, chemoprophylaxis, and spatial distribution of malaria in this

population is scarce. The vast majority of studies about risk factors for contracting malaria and about the efficacy of chemoprophylaxis, eg, have been performed in travelers staying less than 1 month in malaria-endemic areas. Spatial distribution of malaria cases in long-term residents has not been studied at all. With a few notable exceptions, malaria prevention among healthcare

workers has not been thoroughly investigated.15–17 Features unique to this population include relatively well-informed individuals, daily exposure to the consequences of severe malaria, and rapid access to medical care. A previous study demonstrated low compliance with the recommended chemoprophylaxis in UK general practitioners visiting South Asia, but such study has not been performed in sub-Saharan Africa Z-VAD-FMK mw where the risk of acquiring malaria is much higher. Nonimmune healthcare workers in La-Paz Hospital in Bata, in sub-Saharan Equatorial Guinea, provide a unique opportunity for researching malaria prevention and spatial distribution of malaria cases among long-term residents. All foreign staff members were living within the hospital

compound in five different apartment buildings. As a stream which runs just outside the hospital perimeter was the presumed mosquito breeding site, its distance from all apartment buildings was measured (Figure 1). Spatial variations of malaria incidence could thus Liothyronine Sodium be described. In addition, we assessed epidemiological risk factors for acquiring malaria, and compliance of hospital staff members with the recommended personal protective measures and chemoprophylaxis. A cohort study of the risk factors for acquiring malaria was conducted among healthcare personnel residing within the compound of La-Paz Hospital between September 2007 and December 2008. A structured questionnaire was used to assess demographic and epidemiological data. Self-reported compliance with the recommended chemoprophylaxis and personal protective measures was determined. The different chemoprophylaxis regimens that were considered adequate included either mefloquine, doxacycline, or malarone (atovaquone–proguanil). All cases of malaria were diagnosed by a combination of clinical symptoms and at least one confirmatory test performed within the hospital (microscopy, a rapid diagnostic test, or both).

Pooling of samples was carried out to provide sufficient sample v

Pooling of samples was carried out to provide sufficient sample volume for FU determinations. Pooled specimens were analyzed for both total LPV concentration and the FU. Total LPV concentrations for pooled specimens were quantified within the Pediatric Clinical Pharmacology Laboratory at the University of California, San Diego using a validated reverse-phase multiplex high performance liquid chromatography (HPLC) method as previously described [4,5]. Briefly, the method had a lower limit of quantitation (LOQ) adequate for quantitating drug in all collected samples (0.091 μg/mL) and had interassay coefficients of variation (CV) of <11% for the LOQ and all controls. The PB method employed ultrafiltration

(filter units were Micron YM-10 (10 000 MWCO from AMICON, Billercia, MA, USA) and radiolabelled drug (3H) purified and supplied by Abbott Laboratories, Abbott Park, IL, USA (specific Akt inhibitor activity 8.06 Ci/mmol, >99% purity). Pooled plasma samples were centrifuged to remove particulate material. Radiolabel was added to 1 mL of cleared plasma to give an initial concentration of approximately 30 ng/mL. The spiked plasma aliquots were equilibrated for 30 min at 37 °C before ultrafiltration. Spiked plasma (300 μL) was placed into the sample reservoir of the Micron centrifugal filter device and centrifuged for 1 h, at 22 °C, in a fixed head micro centrifuge at high speed,

ADP ribosylation factor around 12 000 × g. Filters were processed in duplicate for each sample. Duplicate aliquots (100 μL) of each spiked plasma and ultrafiltrate Osimertinib research buy sample (200 μL) were radioassayed directly in Cytoscint in a liquid scintillation counter. Since protein is necessary for appropriate filter functioning,

we used an indirect method to assess binding to the filter. We attempted to block the filter units with PEG and tested plasma with 3H LPV. The results showed very low nonspecific binding. This is consistent with Abbott Laboratories’ findings of negligible nonspecific binding (T. Reisch, Metabolic Disease Research, Abbott Laboratories, personal communication). Assay reproducibility was assessed prior to the start of the patient experiments. Six filters were processed with a high LPV spike (approximately 14 500 ng/mL) and five filters were processed using blank (no LPV) plasma. The %CV for the filtrate DPM (disintegrations per minute) was <5%. The experiment was repeated in the middle of the testing period and the %CV for filtrate (five filters) DPM was also <5%. Additionally the high control and blank plasma were processed in duplicate with each batch of subject samples. The mean %bound showed %CV of <0.1 (n=8 testing dates). FU was calculated according to the following formulas: AAG was determined using an FDA approved kit [Human AAG RID (Radial Immunodiffusion) Kit, The Binding Site Inc., San Diego, USA).

We fully agree with Hagmann and colleagues regarding the need to

We fully agree with Hagmann and colleagues regarding the need to further assess the positive isolated anti-HBc, and support the management strategy that they highlighted to identify possible situations of viral reactivation. “
“The increase in the life expectancy achieved following the introduction

of more effective antiretroviral therapy (ART) in recent years now means that the HIV-infected population are for the first time being exposed to the age-related diseases that affect the general population. Nevertheless, the prevalence of these diseases (which include cardiovascular disease, dyslipidaemia, glucose intolerance and diabetes) is higher, and their onset earlier in the HIV population, probably due to the complex interplay between HIV infection, coinfection with hepatitis B and C, and ART. As a result, HIV

physicians are Ipilimumab supplier now required to adopt a new approach to the management of HIV, which involves screening and regular monitoring of all HIV-infected individuals for the presence of comorbidities and prompt referral to other clinical specialties when required. If this challenge to patient management is to be overcome, it is clear that educating physicians in the diagnosis and treatment of age-associated comorbidities selleck chemicals is essential, either through ongoing programmes such as the HIV and the Body initiative, an overarching independent medical education programme established in 2007 and overseen by an independent Steering Committee, organized and funded by Gilead, and/or through N-acetylglucosamine-1-phosphate transferase internal training. To assist in this process, this article provides an overview of common comorbidities affecting HIV-infected persons and provides practical guidance on their management. The introduction of effective combination antiretroviral therapy (ART) for the treatment of HIV infection means that patients now have much greater life expectancies [1]. However, mortality rates for HIV-infected patients are three to 15 times

higher than those of the general population [2]. While some of this excess mortality can be attributed to immunodeficiency, more than half of these deaths are not AIDS-related [3]. For the first time, HIV-infected patients are being exposed to the age-related diseases that affect the non-HIV-infected population; for example, cardiovascular disease (CVD), dyslipidaemia, glucose intolerance and diabetes. The prevalence of these conditions may be increased by the premature ageing effect of HIV infection on the immune system [4] and may mean that age-related metabolic comorbidities are encountered earlier than in the noninfected population. Progression to severe disease may also be accelerated in HIV-infected patients when compared with the general population as a result of coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) and certain lifestyle factors; for example, cigarette smoking and alcohol consumption [1].

6 years) in the PI group compared with the NNRTI group (353 year

6 years) in the PI group compared with the NNRTI group (35.3 years). The various distinct parameters of apoptosis and viral infection were comparable in the NNRTI- and PI-based treatment groups at baseline. As expected, under successful antiretroviral treatment, the total number of lymphocytes and relative and absolute CD4 T-cell counts increased significantly, with an absolute median increase of 500 cells/μL [interquartile

range (IQR) 270–905 cells/μL] in the PI group and 495 cells/μL (IQR 300–683 cells/μL) in the NNRTI group. The lymphocyte levels of viral Nef mRNA, IFN-α mRNA and IFN-α-inducible MxA mRNA also decreased in both treatment groups, but these changes were not significant except for MxA mRNA in the PI treatment group. No differences between the groups Trichostatin A order in changes in CD4 T-cell counts (relative and absolute), viral activity (Nef) or inflammation (IFN-α and MxA) were observed. Over the study period of 7 years, both treatment groups showed a significant decrease in overall apoptosis [Annexin V+/7-AAD– (per cent of total CD4 T-cells)], as well as in the activity of the click here downstream effector caspase 3/7 and extrinsic apoptosis (caspase 8 activity and TRAIL). The

decrease in FasL mRNA, an inducer of

the extrinsic pathway, was not significant in the PI group. Parameters of intrinsic apoptosis (caspase 9, Bcl-2 protein, Bcl-2 mRNA, Bax mRNA, the lactate-to-pyruvate ratio and the mitochondrial-to-nuclear DNA ratio) changed significantly in the PI group but not Roflumilast in the NNRTI group. However, the most remarkable results obtained related to inter-group differences in the changes. Compared with the NNRTI group, patients treated with the PI-based regimen showed a significantly greater decrease in overall apoptosis and concomitantly significantly greater decreases in proapoptotic parameters of the intrinsic pathway (the mitochondrial-to-nuclear DNA ratio and the lactate-to-pyruvate ratio) and significantly greater increases in antiapoptotic intrinsic markers (Bcl-2 protein, Bcl-2 mRNA and the Bcl-2-to-Bax mRNA ratio). In contrast, changes in parameters of extrinsic apoptosis (caspase 8 activity, TRAIL mRNA and FasL mRNA) showed no differences between the two treatment groups. A multiple stepwise linear regression analysis was conducted to describe predictors of inter-group differences in changes in the mitochondrial-to-nuclear DNA ratio (the primary outcome measure). The following variables were tested: treatment regimen (PI vs.

This allowed us to configure the stimulus such that a peripheral

This allowed us to configure the stimulus such that a peripheral cued location was placed either in the affected

region of visual space during SC inactivation or diametrically opposite it (see Fig. 1B and ‘Results’). We localised the cannula tip within the SC before injection, using several methods. First, we targeted a depth of 1.5–3 mm below the SC surface, corresponding to the intermediate and deep layers of this structure. Second, we recorded activity during saccades consistent with known responses in the SC, which allowed us to confirm both the depth in the SC and our placement within the SC retinotopic map. Third, we used electrical microstimulation to evoke saccades. The current needed ZD1839 mouse to evoke such EPZ015666 saccades (typically 10 μA) provided further evidence of depth in the SC, and the metrics of the evoked saccades indicated the position of our cannula within the retinotopic map. We also oriented the bevel in our injection cannula to aim it towards the caudal SC rather than the rostral SC, a strategy

similar to that described in Zenon & Krauzlis (2012). This allowed us to direct drug spread towards the peripheral SC as much as possible, in order to avoid inactivating the rostral SC, where the motor control of microsaccades might be more directly affected. We injected the entire 0.3–0.5-μL volume of muscimol into the SC slowly, over an interval of ~20–30 min (one pulse of solution every ~2 min until our entire volume was injected). Based on previous experience, this strategy helped to stabilise the behavioral effects of the injections and minimise tissue damage. We then took several measures to confirm that our injections affected the peripheral eccentricities that we were interested in. First, we estimated the extent of drug spread in the SC for

each injection by measuring the peak velocities of visually guided saccades (Lovejoy & Krauzlis, 2010; Zenon & Krauzlis, 2012), and estimating the regions of space for which these peak velocities were reduced relative to pre-injection levels. Examples of such analysis are shown in Fig. 2A for several about injections from each monkey, where each shaded region in the figure shows the area with reduced peak velocities (Lovejoy & Krauzlis, 2010). As can be seen, saccades smaller than ~3–4° in amplitude (often much larger) were not affected, suggesting that muscimol did not dramatically spread towards the rostral SC. Second, we performed several analyses to help confirm that our results in this study were not fully explained only by a rostral spread of muscimol towards the foveal representation in the SC. We did this by analysing the characteristics of microsaccades that occurred within 50 ms from cue onset in our main task of Fig. 1.

Erythromycin-susceptible S pneumoniae isolates were categorized

Erythromycin-susceptible S. pneumoniae isolates were categorized as Group IV. Minimum inhibitory concentration (MIC) was determined by the Clinical and Laboratory Standards Institute (CLSI) (2008) broth microdilution method. In vitro susceptibility was tested for 19 antimicrobial agents including erythromycin, penicillin, amoxicillin–clavulanate, ceftriaxone, cefuroxime, cefixime, cefprozil, cefdinir, imipenem, ertapenem, ciprofloxacin, levofloxacin, moxifloxacin, gatifloxacin, clindamycin, tetracycline, trimethoprim–sulfamethoxazole, OSI-744 order rifampin,

and vancomycin. Three to five colonies from an overnight culture on 5% sheep blood agar plates (Becton-Dickinson, Sparks, MD) were resuspended in 10 mL of brain–heart infusion (BHI) broth (Difco Laboratories, Detroit, MI) and incubated for 6–8 h at 35 °C without shaking. For total viable count determination, a 100-μL aliquot selleck kinase inhibitor was diluted in 1 × phosphate-buffered saline (PBS) and plated onto 5% sheep

blood agar plates. The remaining culture was centrifuged for 5 min at 2500 g. The pellet was resuspended in 200 μL of BHI broth and plated onto 5% sheep blood agar plates containing 2 μg mL−1 rifampin (Sigma-Aldrich, St. Louis, MO). Mutation frequency values are reported as the proportion of rifampin-resistant colonies (detected after 48–72 h of incubation in a 5% CO2 atmosphere) vs. total viable cell counts (O’Neill & Chopra, 2002). Results correspond to the mean value obtained in triplicate experiments. An isolate was considered a mutator strain when its frequency was ≥7.5 × 10−8 (Morosini et al., 2003). Allelic replacement mutagenesis for determination of the recombination rate of S. pneumoniae isolates was performed and competent

cells were prepared as described previously (Song et al., 2005). A spr0476 gene that has already been reported as a nonessential gene was used as a target gene for Cediranib (AZD2171) homologous recombination (Thanassi et al., 2002). Amplification of the left and right flanking regions of spr0476 was performed using two pairs of primers, 0476L-F/L-R (5′-CAT CAG TGG AAG GAA TGG TTG ACC-3′/5′-GAC GAA CTC CAA TTC ACT GTT ATC TAC CCA CAA GAG CTT GA-3′) and 0476R-F/R-R (5′-AGA TTT AGA TGT CTA AAA AGC CAT GAA AAG CGT CGT TTG AC-3′/5′-GTT GCG ATT GCG TCC ACC TCC TCA-3′), generating PCR products of 500 and 430 bp, respectively. Primers 0476L-R and 0476R-F contained 21 nucleotides that are identical to the 5′- and 3′-ends of the kanamycin resistance gene cassette, followed by 23 bp of spr0476 gene-specific sequence. The resulting fused PCR product of 1.8 kb was directly transformed into each S. pneumoniae isolate, and homologous recombination between the construct and spr0476 in the chromosome was forced. Pneumococcal transformation was executed under the conditions described previously (Gutiérrez et al., 2004; Song et al., 2005). To estimate the rate at which the fused PCR products recombine with the chromosomal spr0476 in S.

From month 4 to year 3, 63 (66%) of the patients with the Δ32

From month 4 to year 3, 63 (66%) of the patients with the Δ32

deletion and 264 (52%) of the patients without the deletion had a stable virological response (P=0.02). When the follow-up period was extended (month 4 to year 5), 44 patients (48%) and 168 patients (35%), respectively, were found to have a stable virological response (P=0.01). At year 5, differences were also noted between Δ32/wt and wt/wt patients when patients were categorized according to cART experience: in the cART-naïve subgroup, 51 and 45% of patients, respectively, had a stable response, and in the cART-pretreated subgroup, 46 and 27% of patients, respectively, had a stable response (this difference was significant; PMantel Haentzel=0.02). The percentage of patients with CD4 counts >500 cells/μL did not differ significantly between the Δ32 and wild-type patients; at year 3, 55 and 49% of patients, respectively, had CD4 counts >500 cells/μL selleck inhibitor (P=0.26), and at year 5 these percentages were 52 and Roxadustat solubility dmso 54%, respectively (P=0.73). After adjustment for confounding factors, the Δ32 deletion was significantly associated with a sustained virological response during the period from 4 months to 5 years post-enrolment

(P=0.04), and was nearly significantly associated with a sustained virological response during the period from 4 months to 3 years post-enrolment (P=0.07) (Table 2). In terms of the immunological response, the Δ32 deletion was not significantly associated with a CD4 count >500 cells/μL at year 3 (P=0.78) or at year 5 (P=0.15). Among 609 HIV-1-infected patients started on a PI-containing regimen, the frequency of patients heterozygous for CCR5 Δ32 was 16%: frequencies were 4% for patients born in Africa and 19% for patients born in Europe, similar to findings of previous studies carried Protein tyrosine phosphatase out in similar populations [12,14,16,17]. The CCR5 Δ32 deletion was associated with a better virological response

to cART up to 3 and 5 years. A better virological response did not translate into a significantly better immunological response at any time during the study. At baseline, patients with the Δ32 deletion were older, had higher CD4 cell counts and had lower HIV RNA measurements than patients without the deletion. This might be explained by the effect of the CCR5 Δ32 deletion on the natural evolution of HIV infection before these patients started cART. Indeed, previous studies have shown that the presence of an allele with CCR5 Δ32 confers delayed progression to HIV-1 disease in the absence of cART [3,4]. Furthermore, the effect of the deletion may have contributed to a possible selection bias [19]. Indeed, the patients who could be included in the genetic bank study were those who had survived from 1997 to 2002, they were younger. This bias limits the interpretation of our results, as only those patients with a better prognosis were included in the study.